Tumor-associated monoclonal antibodies are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in two animal model systems: a tumor virus induced leukemia of mice and human tumor xenographs in nude athymic mice. The various cytocidal agents being employed are radioisotopes. Their relative therapeutic efficacy when conjugated to antibodies is being assayed and compared to that of monoclonal antibodies alone. The isotopes to be employed include the highly tumoricidal alpha emitting parent radioisotopes 212Pb or 212Bi. The syntheses of different chelates and radiochemical separations required for these objectives are being devised and reduced to clinical practice. Results from isotopic therapy are being compared with those obtained by use of antibody conjugated toxins or drugs with respect to tumor growth, regression or cure. These studies will provide for human medicine a basis for design of rational therapy of malignancies by selectively targeting cytocidal agents to tumors as well as metastases.